Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

IMPORTANCE: Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE: To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS: One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES: The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS: In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE: Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01327976.

Intermittent Vagal Nerve Block for Improvements in Obesity, Cardiovascular Risk Factors, and Glycemic Control in Patients with Type 2 Diabetes Mellitus: 2-Year Results of the VBLOC DM2 Study.

BACKGROUND: One-year results of the VBLOC DM2 study found that intermittent vagal blocking (VBLOC therapy) was safe among subjects with obesity and type 2 diabetes mellitus (T2DM) and led to significant weight loss and improvements in glycemic parameters and cardiovascular risk factors. Longer-term data are needed to determine whether the results are sustained. METHODS: VBLOC DM2 is a prospective, observational study of 28 subjects with T2DM and body mass index (BMI) between 30 and 40 kg/m(2) to assess mid-term safety and weight loss and improvements in glycemic parameters, and other cardiovascular risk factors with VBLOC therapy. Continuous outcome variables are reported using mixed models. RESULTS: At 24 months, the mean percentage of excess weight loss was 22% (95% CI, 15 to 28, p < 0.0001) or 7.0% total body weight loss (95% CI, 5.0 to 9.0, p < 0.0001). Hemoglobin A1c decreased by 0.6 percentage points (95% CI, 0.2 to 1.0, p = 0.0026) on average from 7.8% at baseline. Fasting plasma glucose declined by 15 mg/dL (95% CI, 0 to 29, p = 0.0564) on average from 151 mg/dL at baseline. Among subjects who were hypertensive at baseline, systolic blood pressure declined 10 mmHg (95% CI, 2 to 19, p = 0.02), diastolic blood pressure declined by 6 mmHg (95% CI, 0 to 12, p = 0.0423), and mean arterial pressure declined 7 mmHg (95% CI, 2 to 13, p = 0.014). Waist circumference was significantly reduced by 7 cm (95% CI, 4 to 10, p < 0.0001) from a baseline of 120 cm. The most common adverse events were mild or moderate heartburn, implant site pain, and constipation. CONCLUSIONS: Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

Sustained Weight Loss with Vagal Nerve Blockade but Not with Sham: 18-Month Results of the ReCharge Trial.

BACKGROUND/OBJECTIVES: Vagal block therapy (vBloc) is effective for moderate to severe obesity at one year. SUBJECTS/METHODS: The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL) and total weight loss (%TWL) in intent-to-treat analyses. At 18 months, 142 (88%) vBloc and 64 (83%) Sham patients remained enrolled in the study. RESULTS: 18-month weight loss was 23% EWL (8.8% TWL) for vBloc and 10% EWL (3.8% TWL) for Sham (P < 0.0001). vBloc patients largely maintained 12-month weight loss of 26% EWL (9.7% TWL). Sham regained over 40% of the 17% EWL (6.4% TWL) by 18 months. Most weight regain preceded unblinding. Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain; 98% of events were reported as mild or moderate and 79% had resolved. CONCLUSIONS: Weight loss with vBloc was sustained through 18 months, while Sham regained weight between 12 and 18 months. vBloc is effective with a low rate of serious complications.

Percutaneous autonomic neural modulation: a novel technique to treat cardiac arrhythmia.

Ablation and anti-arrhythmic medications have shown promise but have been met with varying success and unwanted side effects such as myocardial injury, arrhythmias, and morbidity from invasive surgical intervention. The answer to improving efficacy of ablation may include modulation of the cardiac aspect of the autonomic nervous system. Our lab has developed a novel approach and device to navigate the oblique sinus and to use DC current and saline/alcohol irrigation to selectively stimulate and block the autonomic ganglia found on the epicardial side of the heart. This novel approach minimizes myocardial damage from thermal injury and provides a less invasive and targeted approach. For feasibility, proof-of-concept, and safety monitoring, we carried out canine studies to test this novel application. Our results suggest a safer and less invasive way of modulating arrhythmogenic substrate that may lead to improved treatment of AF in humans.